Spectrotemporal content of human auditory working memory represented in functional connectivity patterns

Recent research suggests that working memory (WM), the mental sketchpad underlying thinking and communication, is maintained by multiple regions throughout the brain. Whether parts of a stable WM representation could be distributed across these brain regions is, however, an open question. We addressed this question by examining the content-specificity of connectivity-pattern matrices between subparts of cortical regions-of-interest (ROI). These connectivity patterns were calculated from functional MRI obtained during a ripple-sound auditory WM task. Statistical significance was assessed by comparing the decoding results to a null distribution derived from a permutation test considering all comparable two- to four-ROI connectivity patterns. Maintained WM items could be decoded from connectivity patterns across ROIs in frontal, parietal, and superior temporal cortices. All functional connectivity patterns that were specific to maintained sound content extended from early auditory to frontoparietal cortices. Our results demonstrate that WM maintenance is supported by content-specific patterns of functional connectivity across different levels of cortical hierarchy.

For the irrelevant item, the largest (but statistically non-significant) decoding accuracy of 0.227, corresponding to p=0.246, was observed for a connectivity pattern involving LMFG, LSPL, RSTC, and the right angular gyrus (RAG), which was not among the patterns yielding significant results for the retro-cued WM item either. Supplementary Table S1. Group means and standard errors of mean (SEM) of decoding accuracies and p-values based on the maximum-statistic permutation test in the 7 connectivity patterns with significant results (Fig. 3). The decoding accuracies of the WM item are compared to those obtained for the uncued, i.e., irrelevant item, which was to be forgotten after the presentation of the retro cue.  Supplementary Fig. S1. The ROI-to-ROI connectivity matrices were calculated using partial correlations across all possible pairs during WM maintenance ( Fig. S1a) and during the inter-trial period ( Fig.   S1b, the last two volume acquisitions before the "ready" cue). The analysis was based on the same residualized fMRI time courses that were utilized for the connectivity-based decoding, averaged within each ROI. To display the results, group-averages of Fisher-transformed correlation coefficients were masked to elements with statistically significant results. During maintenance, a larger number of significant frontoparietal connections were observed with bilateral STCs than with OCs ( Fig. 3). At the same time, the number of significant connections between STC areas and frontoparietal regions appeared to be larger during maintenance than during the precue period. Finally, in both analyses, strong connectivity values were observed between homotopic interhemispheric pairs of ROIs (i.e., RSTC-LSTC, LOC-ROC). Group-average Fisher-transformed partial correlations during the pre-trial period, masked to elements with significant results. Partial correlations were calculated between the ROI-averages of the residualized fMRI time courses that were also used for the connectivity-based MVPA areas. The statistical significance was determined using element-wise paired t-tests corrected for multiple comparisons using the false discovery rate (FDR) procedure of Benjamini and Hochberg (Benjamini and Hochberg, 1995).

Activation based MVPA for irrelevant items.
No statistically significant decoding results were obtained in the activation-based MVPA for the irrelevant items, which were to be forgotten after the presentation of the retrocue (for details, see  Univariate fMRI results. Figure S2 shows examples of two comparisons, including the contrast between all auditory events (both items and the probe of each trial) against fixation, as well as a contrast between activations to the visual retro cue and the visual "ready" cue that was presented at the onset of each task trial (Fig. 1 of the main text).

Supplementary Methods
Univariate fMRI analysis. After cortical surface reconstructions and anatomical normalizations and distortion corrections, fMRI volume time series were motion corrected to common session-based template, realigned temporally to correct for the slice timing differences, coregistered with structural MRIs, intensity normalized, and resampled to the "fsaverage" standard brain surface representation. For the univariate analysis, the data were also smoothed along the surface, with iteration steps corresponding to a 8 mm full-width half maximum kernel.
The data then were entered into a general-linear model (GLM) with the task conditions as explanatory variables.
Supplementary Figure S2. Univariate GLM. (Left) GLM analysis contrasting all auditory stimuli, including items and probes, with fixation. (Right) Comparison between the retro cue and "ready cue". Significant increases of the BOLD signal were found in predominantly left hemispheric frontoparietal regions that were also involved in the functional connectivity patterns revealing WM content in our decoding analysis. The data show the statistical significance of the ininitial random-effects group analysis masked to the clusters with p<0.05 according to the permutation test.